The long-term objectives of this research proposal are to study the biology of T lymphocytes that are reactive with Histoplasma capsulatum. To facilitate these studies, murine T cell clones and T cell hybrids that recognize Histoplasma antigens have been generated. The in vivo immunoregulatory function of T cell clones will be examined as well as their trafficking patterns. The capacity of T cell clones to produce soluble mediators will be studied. In addition, the requirements for Histoplasma antigen presentation to T cell hybrids will be delineated, and the nature of Histoplasma antigen recognized by T cell hybrids will be analyzed. Attempts will be made to generate clonotypic antibodies to T cell clones and T cell hybrids. Both an antisera and a monoclonal antibody will be produced. Clonotypic antibodies will be tested for their capacity to modulate the in vitro responses of Histoplasma-specific T cells. In addition, studies will be conducted to determine if clonotypic antibodies can modify experimental histoplasmosis in mice or if it can vaccinate mice against Histoplasma infection. Finally, clonotypic antibodies will be employed to characterize partially the surface receptor on cloned T cells or T cell hybrids that recognizes Histoplasma capsulatum.

Agency
National Institute of Health (NIH)
Institute
National Institute of Allergy and Infectious Diseases (NIAID)
Type
Modified Research Career Development Award (K04)
Project #
5K04AI000856-04
Application #
3070896
Study Section
Bacteriology and Mycology Subcommittee 2 (BM)
Project Start
1987-09-30
Project End
1992-06-30
Budget Start
1990-09-01
Budget End
1991-08-31
Support Year
4
Fiscal Year
1990
Total Cost
Indirect Cost
Name
University of Cincinnati
Department
Type
Schools of Medicine
DUNS #
City
Cincinnati
State
OH
Country
United States
Zip Code
45221
Allendoerfer, R; Magee, D M; Deepe Jr, G S et al. (1993) Transfer of protective immunity in murine histoplasmosis by a CD4+ T-cell clone. Infect Immun 61:714-8
Deepe, G S (1993) Histoplasma capsulatum and V beta a mice: cellular immune responses and susceptibility patterns. J Med Vet Mycol 31:181-8
Henderson, H M; Deepe Jr, G S (1992) Recognition of Histoplasma capsulatum yeast-cell antigens by human lymphocytes and human T-cell clones. J Leukoc Biol 51:432-6
Gomez, F J; Gomez, A M; Deepe Jr, G S (1992) An 80-kilodalton antigen from Histoplasma capsulatum that has homology to heat shock protein 70 induces cell-mediated immune responses and protection in mice. Infect Immun 60:2565-71
Gomez, F J; Gomez, A M; Deepe Jr, G S (1991) Protective efficacy of a 62-kilodalton antigen, HIS-62, from the cell wall and cell membrane of Histoplasma capsulatum yeast cells. Infect Immun 59:4459-64
Gomez, A M; Rhodes, J C; Deepe Jr, G S (1991) Antigenicity and immunogenicity of an extract from the cell wall and cell membrane of Histoplasma capsulatum yeast cells. Infect Immun 59:330-6
Deepe Jr, G S; Brunner, G D (1990) Functional analysis of Histoplasma capsulatum-reactive T-cell hybridomas. Infect Immun 58:1538-44
Harris, J E; Deepe Jr, G S (1989) Requirements for histoplasmin presentation by accessory cells to a Histoplasma capsulatum-reactive T-cell line. J Leukoc Biol 45:105-13
Harris, J E; Deepe Jr, G S (1988) Characterization of antigenic determinants in histoplasmin that stimulate Histoplasma capsulatum-reactive T cells in vitro. Infect Immun 56:2343-9